Methyl iodide → 2-(Tert-butoxycarbonyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18]([OH:20])=[O:19])[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21]N(C)CCN(C)C.C([Li])(C)(C)C.IC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18]([OH:20])=[O:19])[CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH3:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid (2.25 g) and tetramethylethylenediamine (1.347 mL) in tetrahydrofuran (40 mL) was added dropwise t-butyllithium (1.6M, 15.21 mL) at −78° C. The mixture was stirred at −78° C. for 40 minutes. To the resulting mixture was added iodomethane (5.07 mL) dropwise and the mixture was stirred at −78° C. for 3 hours, followed by stirring at room temperature overnight. The reaction mixture was quenched with saturated ammonium chloride. The reaction mixture was extracted with ethyl acetate (150 mL), washed with brine (40 mL×3), dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, 10% methanol/dichloromethane).
Workup
- stirringthe mixture was stirred at −78° C. for 3 hours
- stirringby stirring at room temperature overnight
- customThe reaction mixture was quenched with saturated ammonium chloride
- extractionThe reaction mixture was extracted with ethyl acetate (150 mL)
- washwashed with brine (40 mL×3)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by flash chromatography (silica gel, 10% methanol/dichloromethane)
Sources & evidence
- ORD record
- ord-83891ec9c62442a485e193c652ef1bb1
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227963B2
Reaction notes
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